DESCRIPTION: (Principal Investigator's) The goal of this project is to develop inexpensive methods for making large amounts of useful drugs. The particular class of compounds that are the focus of this project are the polyketides. These molecules are widely used in clinical practice, particularly as antibiotics. For example, erythromycin is a complex polyketide that has found wide use as an antibiotic, because of its ability to kill bacteria without affecting humans. Physicians use other polyketides as antiviral, antifungal, anticancer and immunosuppressive agents. Although methods do exist for the synthesis of polyketides, the methods described in this proposal are much more applicable to industrial use than existing ones. The most important way in which the proposed chemistry differs from current methods is in the use of a catalytic reaction to prepare the starting materials. Only very small amounts of the catalyst are required in the proposed methods, and it is likely that the catalyst will be reused time and time again. Another advantage of the proposed chemistry is that a number of steps can be run in the same reaction solvent and reactor. This property is very important for industrial syntheses, as each additional solvent and reactor increases the amount of waste and complexity of the process.